biostudies-literatureAshraf-Uz-Zaman MAmerican Cancer SocietyNational Institute of Mental HealthNCI NIH HHSNational Institutes of Health112866https://www.ebi.ac.uk/biostudies/studies/S-EPMC7744370biostudies-literatureUnknown209Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data usEuropean journal of medicinal chemistryDesign, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer.PMC7744370RSG-15-009-01-CDDR01CA2140191R15CA231339-0CPRIT RP170003HHSN-271-2013-00017-CR01 CA226436R01 CA186662R15 CA231339R01 CA214019Shahi SFarshbaf MJSajib MSPutnam WMikelis CMAshraf-Uz-Zaman MGerman NAZhang RKallem RRAkwii RTrippier PCAlvina KWang WfalseDesign, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer.Triple-negative breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approximately one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a molecular target that is affected by the presence of these compounds, confirming our data us2021-01-01T00:00:00Z2021 Jan2026-05-02T11:47:31.282Z2022-02-11T14:23:12.536ZS-EPMC77443703303972210.1016/j.ejmech.2020.112866